Is ADAMTS17 p.Pro57Ser (c.169C>T) pathogenic?

ADAMTS17 p.Pro57Ser (c.169C>T) is classified Uncertain significance in ADAMTS17 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-23). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0112%, amr); Associated with Inborn genetic diseases.

What condition is associated with ADAMTS17 p.Pro57Ser (c.169C>T)?

ADAMTS17 p.Pro57Ser (c.169C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADAMTS17 p.Pro57Ser (c.169C>T) in the general population?

ADAMTS17 p.Pro57Ser (c.169C>T) is ultra-rare (popmax 0.0112%, amr) (gnomAD).

What do computational predictors say about ADAMTS17 p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

ADAMTS17 p.Pro57Ser

c.169C>T · rs993878108 · VCV2171643

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -2.5, phastCons 0.29
Regional constraint	o/e 1.09	unconstrained · MANE · 367 kb · p 0.00029 · regional, not allelic
Overall
CADD	11.47	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% Admixed American · 2/17,788 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000794%

Overall 0.00154% 16/1,037,284 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0112%	8,894
South Asian	0.00441%	22,666
European (non-Finnish)	0.0015%	66,617

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ADAMTS17
Protein: p.Pro57Ser
Coding: c.169C>T
MANE Select: NM_139057
dbSNP: rs993878108
Type: single nucleotide variant
Location: chr15:100341320 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 57: the 'disordered' region

Full ADAMTS17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADAMTS17 p.Pro57= Likely benign ★ same residue
ADAMTS17 p.Ala194Val Uncertain significance ★★ ⚠ same condition
ADAMTS17 p.Ala242Ser Uncertain significance ★★ ⚠ same condition
ADAMTS17 p.Ala253Ser Uncertain significance ★★ ⚠ same condition
ADAMTS17 p.Ala590Val Uncertain significance ★★ ⚠ same condition
ADAMTS17 p.Ala683Thr Uncertain significance ★★ ⚠ same condition
ADAMTS17 p.Ala70Gly Uncertain significance ★★ ⚠ same condition
ADAMTS17 p.Ala71Ser Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/adamts17-p-pro57ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown